Aurora-A promotes tumor progression and remodels the Th2-associated immune microenvironment

This study aimed to elucidate the critical role and molecular mechanisms of Aurora-A in the malignant progression and immune microenvironment remodeling of glioblastoma (GBM). Aurora-A is abnormally overexpressed in GBM and is associated with aggressive clinicopathological features and poor patient prognosis. This study demonstrates that high AURKA expression correlates with adverse molecular subtypes (IDH wild-type, 1p/19q non-codeletion) and serves as an independent prognostic risk factor. Functional assays revealed that knockdown of AURKA significantly inhibits the proliferation and migration of GBM cells. Bioinformatics analysis linked AURKA expression to specific immune infiltration patterns, showing a strong positive correlation with inferred Th2 cell infiltration and a negative correlation with CD8⁺ T cell presence. AURKA knockdown not only inhibited tumor growth but also significantly reduced the expression of Th2-related cytokines and the infiltration of CD4⁺ T cells within the tumor. Mechanistically, Aurora-A activates the NF-κB pathway, leading to upregulation of the Th2-recruiting chemokines CCL22 and CCL17. Recruited Th2-skewed CD4+ T cells secrete IL-4 and IL-13, which in turn promote glioma cell proliferation via the JAK1/STAT6 signaling pathway. This establishes a positive feedback loop that drives tumor progression and immune microenvironment remodeling. These findings reveal a novel non-cell-autonomous role for Aurora-A in promoting an immunosuppressive Th2-skewed microenvironment, providing a rationale for combining Aurora-A inhibitors with immunotherapy to enhance anti-tumor efficacy in GBM.